Combined modality chemoradiation is accepted in today's oncologic community as an effective treatment option for unresectable Stage III NSCLC patients, based on the demonstration of a small but significant survival advantage in several phase III randomized studies. However, the search for optimal chemotherapy and radiation regimens has continued to spawn new clinical trials. These studies have addressed issues of modality sequencing (ie: sequential vs. concurrent chemotherapy and radiation), as well as selection of the most effective chemotherapy agent(s). The "classic" chemoradiation regimen that established the efficacy of cisplatin-based induction chemotherapy followed by external thoracic radiation to 60 Gy was first reported by the CALGB (Dillman et al.) The present study builds upon this traditional approach and evaluates the use of induction chemotherapy with a platinum-taxane combination, followed by either concurrent chemoradiation or radiation alone.

The DFS and remission rates appear to be better with induction chemotherapy followed by radiation and paclitaxel as compared to radiation alone.

A survival advantage is expected based on study results thus far.

Clinical/Scientific Implications

The optimum regimen of non-surgical treatment for locally advanced NSCLC patients is an ongoing quest. It has been shown that concurrent chemoradiation improves median survival compared to sequential administration in patients who are able to tolerate the regimen. This study by the BROCAT group is investigating the role of combining the sequencing concepts by incorporating chemotherapy both before AND during thoracic irradiation. The design of the experimental arm tested here was based on a prior paclitaxel dose-escalation study performed by the same investigators, demonstrating acceptable toxicity and 2-yr survival of ~60% using up to 60 mg/m2 of paclitaxel. Based on the results presented thus far, the addition of paclitaxel to radiation appears to achieve superior results compared to radiation alone. The acceptable toxicity profile further makes this regimen a plausible one, and may in fact lead to changing paradigms in treatment of this patient population. Nonetheless, the results presented here are not based on intent-to-treat analysis, which is typically considered the "gold-standard" of statistical data evaluation. This may warrant further studies in the future to validate the promising findings demonstrated here.